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research, information system, noninvasive diagnosis brain mapping, brain scanning, case hi~'tory, computer graphics / printing, electroencephalography, gene expression, genotype, information retrieval, myoclonus epilepsy, neurogenetics, out- comes research, partial seizure, phenotype, positron emission tomography, telemetry clinical research, human data Institution: University Of California San Francisco 500 Parnassus Ave San Francisco, CA 94143 1999 Radiology 01-Sep-98 31-Aug-02 National Inst Of Neurological Disorders And Stroke IRG: ZMH1 Fiscal Year: Department: Project Start: Project End: ICD: ~ROJECT TITLE QUANTITATION OF DIFFUSION EFFECTS IN MR IMAGING OF BRAIN Grant Number: 2R01NS32024-07 PI Name: Zhong, Jianhui Abstract: This is a competing renewal of a grant that has been funded by the NIH. In the next phase of the project, we plan to continue to achieve the general aims at quantitation of dif- fusion effects in MR imaging of brain. In the past four years since the beginning of the current funding period, great pro- gress has been made in the understanding of molecular diffu- sion in tissues, and in the development of new clinical appli- cations of diffusion-weighted MR imaging. New questions, however, have emerged and new techniques have opened up new opportunities for better quantitation and further develop- ment. In the next phase we plan to develop new spectroscopy and imaging methods, and concentrate on the following areas: (1) Contributions of blood microcirculation and cytoplasmic streaming to apparent diffusion coefficient (ADC). We will develop methods based on the Velocity Exchange Spectros- copy (VEXSY) (Callaghan et al 1995) to detect water move- ment of different degrees of correlation and coherence. (2) Changes in ADC with alterations of properties of cellular compartments associated with brain injury. We will use sig- nals from multiple-quantum transition and VEXSY method to detect water diffusion in different environments under con- trolled cellular morphological changes, and we will measure compartmental tortuosity. (3) Effects of magnetic susceptibil- ity on ADC. New methods will be developed to selectively detect and quantify internal field gradients induced by mag- netic susceptibility distributions. (4) Relationship between the ADC and neuronal electrical activities. We will use elec- trical stimulation of varying duration and intensity to study a rat kindling model of seizures with well characterized ana- tomic and functional network. We will correlate ADC changes with electrophysiological and immunocytochemistry measurements. (5) diffusion anisotropy changes associated with pathologic conditions or cerebral activity. We will use rat kindling and forepaw stimulation models in electrical stimulation studies, and human volunteers in activation stud- ies. In all these areas, we will continue to use computer simulations to help in the experiment design, validation and quantitation of the results. The project will focus on studies with phantoms, animals, and human volunteers to look at biophysical basis of diffusion and its alteration during brain injury, but the outcomes from these studies should have a direct impact on brain diffusing imaging in a wide range of clinical settings. Thesaurus Terms: brain scanning, diffusion, generalized seizure, magnetic resonance imaging, stroke blood flow, brain circulation, brain disorder diagnosis, cell water, diagnosis de- sign/evaluation, diagnosis quality/standard, disease model, kindling, mathematical model, method development, phantom model Aplysia, alternatives to animals in research, bioimaging /biomedical imaging, clinical research, computer simulation, human subject, immunocytochemistry, laboratory rat, nuclear magnetic resonance Institution: Fiscal Year: Department: Project Start: Project End: ICD: IRG: University Of Rochester River Campus Sta Rochester, NY 14627 1999 Radiology 01-May-94 31-Mar-03 National Inst Of Neurological Disorders And Stroke RNM ~ROJECT TITL( QUANTITATIVE ICTAL FLOW CHANGES IN LOCALIZING EPILEPSY Grant Number: 5R01NS35674-02 PI Name: Zubal, George Abstract: DESCRIPTION (Applicant's Abstract): We pro- pose that the site of seizure onset in epilepsy can be imaged by novel analysis of ictal and interictal nuclear medicine to- mographic perfusion scans. The imaging techniques pro- posed here will yield data supporting the hypothesis that the epileptogenic region exhibits a hyperperfusion at seizure on- set; and after a short time after seizure cessation, enters a state of excess hypoperfusion for a short time. WE believe that by analyzing EEG with SPECT difference images, we 777

Project title quantitation of diffusion effects in MR imaging of brain

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research, information system, noninvasive diagnosis brain mapping, brain scanning, case hi~'tory, computer graphics / printing, electroencephalography, gene expression, genotype, information retrieval, myoclonus epilepsy, neurogenetics, out- comes research, partial seizure, phenotype, positron emission tomography, telemetry clinical research, human data

Institution: University Of California San Francisco

500 Parnassus Ave San Francisco, CA 94143 1999 Radiology 01-Sep-98 31-Aug-02 National Inst Of Neurological

Disorders And Stroke IRG: ZMH1

Fiscal Year: Department: Project Start: Project End: ICD:

~ROJECT TITLE

QUANTITATION OF DIFFUSION EFFECTS IN MR IMAGING OF BRAIN

Grant Number: 2R01NS32024-07 PI Name: Zhong, Jianhui

Abstract: This is a competing renewal of a grant that has been funded by the NIH. In the next phase of the project, we plan to continue to achieve the general aims at quantitation of dif- fusion effects in MR imaging of brain. In the past four years since the beginning of the current funding period, great pro- gress has been made in the understanding of molecular diffu- sion in tissues, and in the development of new clinical appli- cations of diffusion-weighted MR imaging. New questions, however, have emerged and new techniques have opened up new opportunities for better quantitation and further develop- ment. In the next phase we plan to develop new spectroscopy and imaging methods, and concentrate on the following areas: (1) Contributions of blood microcirculation and cytoplasmic streaming to apparent diffusion coefficient (ADC). We will develop methods based on the Velocity Exchange Spectros- copy (VEXSY) (Callaghan et al 1995) to detect water move- ment of different degrees of correlation and coherence. (2) Changes in ADC with alterations of properties of cellular compartments associated with brain injury. We will use sig- nals from multiple-quantum transition and VEXSY method to detect water diffusion in different environments under con- trolled cellular morphological changes, and we will measure compartmental tortuosity. (3) Effects of magnetic susceptibil- ity on ADC. New methods will be developed to selectively detect and quantify internal field gradients induced by mag- netic susceptibility distributions. (4) Relationship between the ADC and neuronal electrical activities. We will use elec-

trical stimulation of varying duration and intensity to study a rat kindling model of seizures with well characterized ana- tomic and functional network. We will correlate ADC changes with electrophysiological and immunocytochemistry measurements. (5) diffusion anisotropy changes associated with pathologic conditions or cerebral activity. We will use rat kindling and forepaw stimulation models in electrical stimulation studies, and human volunteers in activation stud- ies. In all these areas, we will continue to use computer simulations to help in the experiment design, validation and quantitation of the results. The project will focus on studies with phantoms, animals, and human volunteers to look at biophysical basis of diffusion and its alteration during brain injury, but the outcomes from these studies should have a direct impact on brain diffusing imaging in a wide range of clinical settings.

Thesaurus Terms: brain scanning, diffusion, generalized seizure, magnetic resonance imaging, stroke blood flow, brain circulation, brain disorder diagnosis, cell water, diagnosis de- sign/evaluation, diagnosis quality/standard, disease model, kindling, mathematical model, method development, phantom model Aplysia, alternatives to animals in research, bioimaging /biomedical imaging, clinical research, computer simulation, human subject, immunocytochemistry, laboratory rat, nuclear magnetic resonance

Institution:

Fiscal Year: Department: Project Start: Project End: ICD:

IRG:

University Of Rochester River Campus Sta Rochester, NY 14627 1999 Radiology 01-May-94 31-Mar-03 National Inst Of Neurological

Disorders And Stroke RNM

~ROJECT TITL(

QUANTITATIVE ICTAL FLOW CHANGES IN LOCALIZING EPILEPSY

Grant Number: 5R01NS35674-02 PI Name: Zubal, George

Abstract: DESCRIPTION (Applicant's Abstract): We pro- pose that the site of seizure onset in epilepsy can be imaged by novel analysis of ictal and interictal nuclear medicine to- mographic perfusion scans. The imaging techniques pro- posed here will yield data supporting the hypothesis that the epileptogenic region exhibits a hyperperfusion at seizure on- set; and after a short time after seizure cessation, enters a state of excess hypoperfusion for a short time. WE believe that by analyzing EEG with SPECT difference images, we

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